The serine/threonine kinase IL-1R-associated kinase (IRAK)4 is a critical regulator of innate immunity. We have identified BMS-986126, a potent, highly selective inhibitor of IRAK4 kinase activity ...that demonstrates equipotent activity against multiple MyD88-dependent responses both in vitro and in vivo. BMS-986126 failed to inhibit assays downstream of MyD88-independent receptors, including the TNF receptor and TLR3. Very little activity was seen downstream of TLR4, which can also activate an MyD88-independent pathway. In mice, the compound inhibited cytokine production induced by injection of several different TLR agonists, including those for TLR2, TLR7, and TLR9. The compound also significantly suppressed skin inflammation induced by topical administration of the TLR7 agonist imiquimod. BMS-986126 demonstrated robust activity in the MRL/lpr and NZB/NZW models of lupus, inhibiting multiple pathogenic responses. In the MRL/lpr model, robust activity was observed with the combination of suboptimal doses of BMS-986126 and prednisolone, suggesting the potential for steroid sparing activity. BMS-986126 also demonstrated synergy with prednisolone in assays of TLR7- and TLR9-induced IFN target gene expression using human PBMCs. Lastly, BMS-986126 inhibited TLR7- and TLR9-dependent responses using cells derived from lupus patients, suggesting that inhibition of IRAK4 has the potential for therapeutic benefit in treating lupus.
Hydrophobic anticancer drug, raloxifene hydrochloride (RH) is intercalated into a series of magnesium aluminum layered double hydroxides (LDHs) with various charge density anions through ion exchange ...technique for controlled drug delivery. The particle nature of the LDH in presence of drug is determined through electron microscopy and surface morphology. The release of drug from the RH intercalated LDHs was made very fast or sustained by altering the exchangeable anions followed by the modified Freundlich and parabolic diffusion models. The drug release rate is explained from the interactions between the drug and LDHs along with order–disorder structure of drug intercalated LDHs. Nitrate bound LDH exhibits greater interaction with drug and sustained drug delivery against the loosely interacted phosphate bound LDH-drug, which shows fast release. Cell viability through MTT assay suggests drug intercalated LDHs as better drug delivery vehicle for cancer cell line against poor bioavailability of the pure drug. In vivo study with mice indicates the differential tumor healing which becomes fast for greater drug release system but the body weight index clearly hints at damaged organ in the case of fast release system. Histopathological experiment confirms the damaged liver of the mice treated either with pure drug or phosphate bound LDH-drug, fast release system, vis-à-vis normal liver cell morphology for sluggish drug release system with steady healing rate of tumor. These observations clearly demonstrate that nitrate bound LDH nanoparticle is a potential drug delivery vehicle for anticancer drugs without any side effect.
Drug intercalated layered double hydroxide as the novel carrier for anti-cancer drug without any side effect against poor bioavailability and remarkable side effect of pure drug. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
The increasing popularity of wearable electronics has sparked interest in flexible energy harvesters as alternatives to conventional batteries. Flexible magnetoelectric (ME) composites, known for ...converting ambient magnetic field energy into useable power, are emerging as promising autonomous energy sources for integration into wearable devices. In this study, we prepared flexible (PVDF-AlN)–(NiO–CNF) based ME composites using two different methods: solution-casting and electrospinning techniques. The ME coupling was confirmed by measuring the ferroelectric and magnetic properties of the composite, and it was qualitatively characterized through the ME coupling coefficient. The electrospinning fibers-based ME composite exhibited an optimal value of 10.6 V/cm.Oe, significantly higher than the solution-casting films-based ME composite (1.3 V/cm.Oe) under a 1 kHz AC magnetic field (off-resonance condition). Subsequently, a flexible magneto-mechano-electric (MME) generator was designed using electrospun-derived material, harvesting a sinusoidal wave with a maximum output peak-to-peak voltage of 9.02 V. The generator displayed an optimal DC power density of 97 μW/m2 when exposed to a weak AC magnetic field of 6 Oe at a frequency of 50 Hz. Consequently, it holds great promise as an efficient autonomous power supply for medical sensing and various miniature electronic applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Leiomyomas are the most common benign tumours of oesophageal smooth muscle origin. In this era of constantly evolving medical technology, video-assisted, robot-assisted and endoscopic approaches are ...the minimally invasive strategies for the excision of these lesions. Here, we report our modification of this surgery. The lesion was excised with uniportal video-assisted thoracoscopic surgery in a semi-prone position with single-lumen endobronchial intubation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The recent emergence of pink bollworm (PBW), Pectinophora gossypiella (Saunders) has posed serious ecological and economic implications for cotton production in India since 2017. The project ...“Insecticide Resistance Management (IRM): Dissemination of pink bollworm management strategies in Bt-cotton” was implemented consecutively for four years from 2018 -19, 2019–20, 2020-21 and 2021-22 in 21 districts across three cotton growing zones of the country. In each year, field demonstrations were conducted on 1050 acres of cotton area and mass awareness was created through outreach activities. With concerted and focused efforts, the PBW infestations could be brought down by 42.75% in 2018–19, 43.49% in 2019–20, 35.55% in 2020-21 and 33.77% in 2021-22 in the demonstration plots over the farmer practices. An increased benefit: cost ratios of 2.16:1, 2:1, 1.89:1 and 2.24:1 were realized during 2018–19, 2019–20, 2020-21 and 2021–22, respectively. Similarly, the average number of sprays for the control of cotton pests during the season was reduced to 5.02, 4.94, 5.19 and 5.18 in integrated pest management (IPM) fields as compared to 6.98, 7.66, 8.07 and 8.20 in non-integrated pest management (NIPM) fields in the corresponding years. Reduction in pesticide usage in IPM vs NIPM fields was 46.39% in terms of cost, and 38.96% in terms of volume during 2019-20 while concurrent percent reduction in pesticide usage was 41.03 & 39.33 during 2020-21 and 40.70 & 39.38 in 2021–22. Comparatively more seed cotton was harvested from IPM than NIPM fields i.e. 2190 vs 1820 kg/ha in 2018–19, 2049 vs 1715 kg/ha in 2019–20, 1881 vs 1585 kg/ha in 2020-21 and 1901 vs 1607 kg/ha in 2021–22. Significant success in reducing PBW infestation, pesticide usage and corresponding improvement in yield, economic benefits and environmental quality in terms of reduced EIQFUR has been achieved through IPM demonstrations. This area-wide success was achieved through collective efforts and active involvement of all concerned stakeholders.
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•Pink bollworm has emerged as serious threat to Indian cotton production.•Areawide IPM strategies disseminated & mass awareness created through outreach.•Significant reduction in pest infestation and pesticide usage was achieved.•Realization of economic benefits to cotton growers was demonstrated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Leiomyomas are the most common benign tumours of oesophageal smooth muscle origin. In this era of constantly evolving medical technology, video-assisted, robot-assisted and endoscopic approaches are ...the minimally invasive strategies for the excision of these lesions. Here, we report our modification of this surgery. The lesion was excised with uniportal video-assisted thoracoscopic surgery in a semi-prone position with single-lumen endobronchial intubation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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